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J Cell Biol. 2015 Mar 16;208(6):671-81. doi: 10.1083/jcb.201410047.

The nucleoporin gp210/Nup210 controls muscle differentiation by regulating nuclear envelope/ER homeostasis.

Author information

1
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037 Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
2
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037 hetzer@salk.edu.

Abstract

Previously, we identified the nucleoporin gp210/Nup210 as a critical regulator of muscle and neuronal differentiation, but how this nucleoporin exerts its function and whether it modulates nuclear pore complex (NPC) activity remain unknown. Here, we show that gp210/Nup210 mediates muscle cell differentiation in vitro via its conserved N-terminal domain that extends into the perinuclear space. Removal of the C-terminal domain, which partially mislocalizes gp210/Nup210 away from NPCs, efficiently rescues the differentiation defect caused by the knockdown of endogenous gp210/Nup210. Unexpectedly, a gp210/Nup210 mutant lacking the NPC-targeting transmembrane and C-terminal domains is sufficient for C2C12 myoblast differentiation. We demonstrate that the endoplasmic reticulum (ER) stress-specific caspase cascade is exacerbated during Nup210 depletion and that blocking ER stress-mediated apoptosis rescues differentiation of Nup210-deficient cells. Our results suggest that the role of gp210/Nup210 in cell differentiation is mediated by its large luminal domain, which can act independently of NPC association and appears to play a pivotal role in the maintenance of nuclear envelope/ER homeostasis.

PMID:
25778917
PMCID:
PMC4362455
DOI:
10.1083/jcb.201410047
[Indexed for MEDLINE]
Free PMC Article

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